CN108853583A - A kind of peripheral nerve bracket and preparation method thereof based on 3D printing - Google Patents
A kind of peripheral nerve bracket and preparation method thereof based on 3D printing Download PDFInfo
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- CN108853583A CN108853583A CN201810657502.XA CN201810657502A CN108853583A CN 108853583 A CN108853583 A CN 108853583A CN 201810657502 A CN201810657502 A CN 201810657502A CN 108853583 A CN108853583 A CN 108853583A
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- peripheral nerve
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/56—Porous materials, e.g. foams or sponges
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/20—Polysaccharides
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/222—Gelatin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/22—Polypeptides or derivatives thereof, e.g. degradation products
- A61L27/24—Collagen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3604—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the human or animal origin of the biological material, e.g. hair, fascia, fish scales, silk, shellac, pericardium, pleura, renal tissue, amniotic membrane, parenchymal tissue, fetal tissue, muscle tissue, fat tissue, enamel
- A61L27/3633—Extracellular matrix [ECM]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/36—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix
- A61L27/3641—Materials for grafts or prostheses or for coating grafts or prostheses containing ingredients of undetermined constitution or reaction products thereof, e.g. transplant tissue, natural bone, extracellular matrix characterised by the site of application in the body
- A61L27/3675—Nerve tissue, e.g. brain, spinal cord, nerves, dura mater
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y10/00—Processes of additive manufacturing
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- B—PERFORMING OPERATIONS; TRANSPORTING
- B33—ADDITIVE MANUFACTURING TECHNOLOGY
- B33Y—ADDITIVE MANUFACTURING, i.e. MANUFACTURING OF THREE-DIMENSIONAL [3-D] OBJECTS BY ADDITIVE DEPOSITION, ADDITIVE AGGLOMERATION OR ADDITIVE LAYERING, e.g. BY 3-D PRINTING, STEREOLITHOGRAPHY OR SELECTIVE LASER SINTERING
- B33Y80/00—Products made by additive manufacturing
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/40—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a specific therapeutic activity or mode of action
- A61L2300/412—Tissue-regenerating or healing or proliferative agents
- A61L2300/414—Growth factors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L2430/00—Materials or treatment for tissue regeneration
- A61L2430/32—Materials or treatment for tissue regeneration for nerve reconstruction
Abstract
The invention discloses a kind of peripheral nerve bracket based on 3D printing, the filler including outer tube and in outer tube, filler are three-dimensional frameworks made of gauze curling, and gauze is made of bio-ink；The invention also discloses the preparation methods of peripheral nerve bracket.There is the structure of natural environment nerve and the bionical element of composition using peripheral nerve bracket prepared by method of the invention；On the basis of the outer tube of Electrospun material guarantees bio-compatible, the abundant structural stability of bracket is provided, filler can be reduced in the fabrication process to ink shaping strength requirement, expand the selection range of filler, so that ink can choose more biological functions；The present invention provides corresponding biological characteristics by the way that specific function component is perfused or infiltrated to skeleton, for filler, for example promotes the growth of aixs cylinder, promotes vascularization.
Description
Technical field
The present invention relates to organizational project and biomimetic features technical field, especially a kind of peripheral branches based on 3D printing
Frame and preparation method thereof.
Background technique
Perineural anatomical structure is complicated, is divided into perilemma epineurium area, nerve tract area and neural comma field etc., each region
The functional structures such as capilary, connective tissue are inside also distributed with.In addition, the constituent and spatial distribution of different zones are also very multiple
It is miscellaneous.Current nerve repair material (or conduit) reported in the literature is mainly prepared using single homogeneous material (such as synthetic material, natural
Material removes cell matrix materials), according to the principle of nerve regneration, the structure and composition of conduit have also carried out Bionic Design (such as mind
Through growth factor gradient distribution etc.), but this kind of bracket is still more single in composition and structure, can not embody natural nerve
Complexity composition and structure.
Biological 3D printing technique compares conventional machining techniques, the manufacture and different component space for complex organization's structure point
Cloth has significant advantage.3D printing most importantly bio-ink.Thermoplastic degradable poly ether-ether material, although printing work
Skill is mature, stablizes after printing, but it is larger with perineural differences of mechanical properties, and the print conditions of high temperature are difficult to realize pair
The load of cell or activated protein.And the bio-ink strength of materials that is suitable for cell growth it is universal it is lower, stability is bad, it is difficult to
Meets the needs of stability in direct printing shaping and later period use.Still use biocompatibility good without more perfect at present
The technique of good Hydrogels ink material 3D printing peripheral nerve bracket.
Summary of the invention
Based on the above issues, one kind is provided and is based on it is an object of the invention to overcome above-mentioned the deficiencies in the prior art place
The peripheral nerve bracket of external structure and 3D printing technique made of degradable polymer, has both bioactive functions and structure is steady
It is qualitative.
To achieve the above object, the technical scheme adopted by the invention is as follows：A kind of peripheral nerve bracket based on 3D printing, packet
Outer tube and the filler in the outer tube are included, the filler is three-dimensional framework made of gauze curling, the yarn
Net is made of bio-ink.
Wherein, the network of (two dimension) gauze is rectangle, can also be adjusted to prismatic, square, parallel as needed
The intensity of three-dimensional framework, the permeability of vertical and horizontal can be changed by adjusting the size and shape of gauze grid in quadrangle etc.
(guidance aixs cylinder oriented growth physical signal is provided)；The structure of filler has copied nerve regneration region；Three-dimensional framework has more
Pore structure, is conducive to the immersion of the gel rubber material or solution with certain biological function, to introduce particular organisms function or micro-
See structure.
Preferably, the outer tube is made of Electrospun.Wherein, Electrospun preferably use PLGA, PLLA, PCL,
At least one of PTMC, gelatin, chitosan are made, and outer tube can be degraded in animal body as a result,；Outside Electrospun material
The preparation of disk receiver can be used in casing.
Preferably, the gauze is made of 3D printing method.
Preferably, the bio-ink contain acrylic double bond terminal groups modification PEG preparation hydrogel, natural material and
Organize at least one of de- cell hydrogel.
Preferably, the natural material is acrylic acid or hyaluronic acid, gelatin or collagen that norbornene is modified.
Preferably, the tissue is peripheral nerve, spinal cord, submucous layer of small intestine, umbilical cord, placenta or amnion.It is highly preferred that
Tissue is originated from people or pig.
Preferably, the gel or solution that can promote axon growth or vascularization are perfused or are impregnated on the three-dimensional framework.
Wherein, the gel or solution for promoting vascularization preferably comprise VEGF.
Preferably, it is perfused or is impregnated with the solution containing β-NGF on the three-dimensional framework, to promote axon growth；Or
The hydrogel that the peripheral nerve in pig source obtains after taking off cell, crushing through pepsin digestion.
As another aspect of the present invention, the system of the present invention also provides a kind of peripheral nerve bracket based on 3D printing
Preparation Method includes the following steps：
(1) outer tube of Electrospun material is provided；
(2) two-dimentional gauze is prepared using with temperature, the ink of ultraviolet light sensitive characteristic and 3D printing method, wherein
3D printing barrel temperature is 24~28 DEG C, and the control of forming area temperature is 4~12 DEG C；
(3) two-dimentional gauze obtained by step (2) is kept to use light intensity for 0.1~3mv/cm in above-mentioned low temperature environment2's
365nm UV irradiates 8s~2min；Then, by crimping or cutting superposition, three-dimensional framework is made；The two dimension of printing shaping as a result,
Polymer can be chemically crosslinked in screen structure, improve the stability of the two-dimentional gauze soft model printed；
(4) use concentration for the solution or/and mass concentration of the nervegrowthfactor-β-NGF of the μ of 100pg/ml~10 g/ml
For 0.1~10% pig source peripheral nerve through taking off cell, the hydrogel obtained through pepsin digestion after crushing infiltration or
Person is filled into three-dimensional framework obtained by step (3), is then loaded into the outer tube of the Electrospun material, and the surrounding mind is made
Through bracket.
Wherein, ink contains the de- cell of hydrogel, natural material and tissue of acrylic double bond terminal groups modification PEG preparation
At least one of hydrogel；Natural material is preferably acrylic acid or hyaluronic acid, gelatin or collagen that norbornene is modified；Step
Suddenly in (2), the two-dimentional gauze model of printing, the initial temperature sensitivity printing shaping for utilizing ink can be designed according to demand；Step
Suddenly in (4), by infiltrating or being perfused, the modification of biology is carried out, to bracket in favor of the elongation growth of neural axon.
In conclusion beneficial effects of the present invention are：
(1) structure and composition of the peripheral nerve bracket of the invention based on 3D printing with natural environment nerve is bionical
Element；
(2) on the basis of Electrospun outer tube guarantees bio-compatible, provide bracket abundant structural stability, filler is manufacturing
It can be reduced in the process to ink shaping strength requirement, expand the selection range of filler, so that ink can choose more
Biological function, Electrospun can degrade in vivo；
(3) 3D printing two dimension gauze is used, be then superimposed or is crimped as filler skeleton, skeleton can be accurately regulated and controled
Structure and permeability；
(4) present invention provides corresponding biological characteristics by the way that specific function component is perfused or infiltrated to skeleton for filler
Property, for example promote the growth of aixs cylinder, promote vascularization；
(5) structure of the invention and preparation method are simple, easily realize.
Detailed description of the invention
Fig. 1 is the preparation flow schematic diagram of the peripheral nerve bracket of the invention based on 3D printing；
Fig. 2 is the electronic scanner microscope figure observed during preparation peripheral nerve bracket of the present invention, wherein A is
3D printing two dimension gauze and it is curled into skeleton；B is Electrospun outer tube；C is the transversal of the peripheral nerve bracket before perfusion/infiltration
Face；D is the vertical section electronic scanner microscope figure of the peripheral nerve bracket before perfusion/infiltration；
Wherein, 1, outer tube, 2, three-dimensional framework, 3, gauze, 4,3D printer, 5, the peripheral branches before perfusion/infiltration
The cross-sectional view of frame, 6, the cross-sectional view of peripheral nerve bracket after perfusion/infiltration.
Specific embodiment
Present inventor manufactures two-dimentional screen structure using 3D printing technique, wherein structural unit according to demand may be used
It is designed as different shape, then, realizes the preparation of three-dimensional framework by crimping or being superimposed；For the three-dimensional framework for maintaining printing
The stabilization of environment in structure, reduces the generation of scar, improves the operability of clinical application, by the skeleton structure of 3D printing and electricity
Spinning outer tube is assembled into the bracket with tube core structure；For the biological function for improving bracket, it can further pass through perfusion or leaching
Moisten the gel rubber material or solution with certain biological function.
The 3D printing filler of the application is the soft gel ink material that can promote axon growth, is gone out with this ink printed
The elongated peripheral nerve bracket of 0-5cm self-supporting and stability, be unable to reach test and clinic to structural stability
It is required that so, it is matched with Electrospun outer tube, 3D printing filler is placed in outer tube, is assembled into tube core structure
Peripheral nerve bracket.
The application utilizes 3D printing technique, is prepared for having both around biological function and structural stability by bionics techniques
Nerve Scaffold；Specifically, peripheral nerve bracket of the invention has the following advantages that：
1, bionic structure, outer tube are to maintain bracket shape stability and operate convenient for clinical suture, and filler is nerve
Regeneration provides microenvironment；
2, outer tube selects Electrospun to be made, and takes into account biocompatibility and structural stability；Electrospun is easy to process, in body
It is interior degradable, it can be accurately adjusted parameter, such as Electrospun composition, the bore dia of porous structure, consistency etc.；
3, it chooses with the better soft material of the matched biocompatibility of peripheral nerve mechanical property as 3D printing ink, passes
The peripheral nerve conduit of system technique preparation must satisfy certain mechanical property then to maintain stability, therefore, mechanical property one
As to be much higher than natural peripheral nerve.In addition, the compound ink in the present invention includes being conducive to molding modified gel and surrounding
Neural de-cellular system hydrogel, having taken into account 3D can print property and special bioactivity；
4, since tissue engineering bracket will fully consider the conveying of nutrition, the design of structural unit is adjustable in the application
The permeability (passing through grid) of material, conducive to the conveying of substance；In addition, three-dimensional framework can uniformly or the load biology of gradient is believed
Number molecule realizes that the spatial distribution of signal, guidance aixs cylinder orientation extend；
5, the structure and permeability of bracket be can be adjusted according to the needs；
6, can also be added in three-dimensional framework of the invention can promote axon growth vigor or raising blood vessel to grow into the life of speed
Object bioactive molecule is conducive to long section neurologic defect reparation to improve the survival proliferation of early stage cell.
To better illustrate the object, technical solutions and advantages of the present invention, below in conjunction with the drawings and specific embodiments pair
The present invention is described further.Unless otherwise instructed, the technology in the application, such as the preparation and 3D printing skill of Electrospun casing
Art, belongs to techniques well known, and those of ordinary skill in the art combine the relevant technologies side in well-known technique and the application
Case does not need to pay creative work, corresponding structure or product can be realized.
Embodiment 1
As shown in Figure 1, a kind of embodiment of the peripheral nerve bracket of the invention based on 3D printing, including 1 He of outer tube
Filler in outer tube 1, filler are three-dimensional frameworks 2 made of gauze 3 crimps, and gauze 3 is made of bio-ink,
Outer tube 1 is made of Electrospun, and Electrospun is made of PLGA, and gauze 3 is made of 3D printing method.
Wherein, bio-ink is the hydrogel of acrylic double bond terminal groups modification PEG preparation；It is perfused or infiltrates on three-dimensional framework
There is the solution that can promote axon growth, wherein containing β-NGF.
The preparation method of above-mentioned peripheral nerve bracket, includes the following steps：
(1) outer tube of Electrospun material is provided；
(2) using with temperature, the ink (i.e. bio-ink) of ultraviolet light sensitive characteristic and 3D printing method preparation two
Tie up gauze, wherein 3D printing barrel temperature is 24 DEG C, and the control of forming area temperature is 6 DEG C；
(3) two-dimentional gauze obtained by step (2) is kept to use light intensity for 3mv/cm in above-mentioned low temperature environment2365nm UV
Irradiate 8s；Then, by crimping or cutting superposition, three-dimensional framework is made；
(4) concentration is used as the solution impregnation of the nervegrowthfactor-β-NGF of 100pg/ml or is filled into step (3) institute
Three-dimensional framework is obtained, is then loaded into the outer tube of the Electrospun material, the peripheral nerve bracket is made.
Later, peripheral nerve bracket is freeze-dried, peripheral nerve bracket is observed by scanning electron microscope (SEM)
Macro, microstructure, as shown in Figure 2.
Embodiment 2
A kind of embodiment of peripheral nerve bracket based on 3D printing of the invention, including outer tube 1 and be set to outer tube 1
Interior filler, filler are three-dimensional frameworks 2 made of gauze 3 crimps, and gauze 3 is made of bio-ink, and outer tube 1 uses
Electrospun is made, and Electrospun is made of PLLA and PCL, and gauze is made of 3D printing method.
Wherein, bio-ink is acrylic acid or the hyaluronic acid that norbornene is modified；It is perfused or is impregnated on three-dimensional framework
The hydrogel that the peripheral nerve in pig source obtains after taking off cell, crushing through pepsin digestion.
The preparation method of above-mentioned peripheral nerve bracket, includes the following steps：
(1) outer tube of Electrospun material is provided；
(2) using with temperature, the ink (i.e. bio-ink) of ultraviolet light sensitive characteristic and 3D printing method preparation two
Tie up gauze, wherein 3D printing barrel temperature is 25 DEG C, and the control of forming area temperature is 4 DEG C；
(3) two-dimentional gauze obtained by step (2) is kept to use light intensity for 1.5mv/cm in above-mentioned low temperature environment2365nm
UV irradiates 25s；Then, by crimping or cutting superposition, three-dimensional framework is made；
(4) use mass concentration for 0.1~10% pig source peripheral nerve after de- cell, crushing through pepsin
It digests obtained hydrogel infiltration or is filled into three-dimensional framework obtained by step (3), be then loaded into the Electrospun material
In outer tube, the peripheral nerve bracket is made.
Later, peripheral nerve bracket is freeze-dried, peripheral nerve bracket is observed by scanning electron microscope (SEM)
Macro, microstructure, as shown in Figure 2.
Embodiment 3
A kind of embodiment of peripheral nerve bracket based on 3D printing of the invention, including outer tube 1 and be set to outer tube 1
Interior filler, filler are three-dimensional frameworks 2 made of gauze curling, and gauze 3 is made of bio-ink, and outer tube 1 uses
Electrospun is made, and Electrospun is made of PTMC, and gauze is made of 3D printing method.
Wherein, bio-ink is that tissue takes off cell hydrogel；Tissue is peripheral nerve, spinal cord, the mucous membrane of small intestine in pig source
Lower layer, umbilical cord, placenta or amnion；The solution containing β-NGF that can promote axon growth is perfused or is impregnated on three-dimensional framework.
The preparation method of above-mentioned peripheral nerve bracket, includes the following steps：
(1) outer tube of Electrospun material is provided；
(2) using with temperature, the ink (i.e. bio-ink) of ultraviolet light sensitive characteristic and 3D printing method preparation two
Tie up gauze, wherein 3D printing barrel temperature is 27 DEG C, and the control of forming area temperature is 12 DEG C；
(3) two-dimentional gauze obtained by step (2) is kept to use light intensity for 0.7mv/cm in above-mentioned low temperature environment2365nm
UV irradiates 1min；Then, by crimping or cutting superposition, three-dimensional framework is made；
(4) concentration is used as the solution impregnation of the nervegrowthfactor-β-NGF of 1 μ g/ml or is filled into obtained by step (3)
Then three-dimensional framework is loaded into the outer tube of the Electrospun material, the peripheral nerve bracket is made.
Later, peripheral nerve bracket is freeze-dried, peripheral nerve bracket is observed by scanning electron microscope (SEM)
Macro, microstructure, as shown in Figure 2.
Embodiment 4
A kind of embodiment of peripheral nerve bracket based on 3D printing of the invention, including outer tube 1 and be set to outer tube 1
Interior filler, filler are three-dimensional frameworks 2 made of gauze 3 crimps, and gauze 3 is made of bio-ink, and outer tube 1 uses
Electrospun is made, and Electrospun is made of PLGA, gelatin and chitosan, and gauze 3 is made of 3D printing method.
Wherein, the hydrogel and organize de- cell water-setting that bio-ink contains acrylic double bond terminal groups modification PEG preparation
Glue；Tissue is peripheral nerve, spinal cord, submucous layer of small intestine, umbilical cord, placenta or the amnion in pig source；On three-dimensional framework perfusion or
The peripheral nerve for being impregnated with the solution containing β-NGF and pig source that can promote axon growth passes through after de- cell, crushing
The hydrogel that pepsin digestion obtains.
The preparation method of above-mentioned peripheral nerve bracket, includes the following steps：
(1) outer tube of Electrospun material is provided；
(2) using with temperature, the ink (i.e. bio-ink) of ultraviolet light sensitive characteristic and 3D printing method preparation two
Tie up gauze, wherein 3D printing barrel temperature is 28 DEG C, and the control of forming area temperature is 9 DEG C；
(3) two-dimentional gauze obtained by step (2) is kept to use light intensity for 0.1mv/cm in above-mentioned low temperature environment2365nm
UV irradiates 2min；Then, by crimping or cutting superposition, three-dimensional framework is made；
(4) using concentration for the solution of the nervegrowthfactor-β-NGF of 10 μ g/ml and mass concentration is 0.1~10%
Pig source peripheral nerve by taking off cell, the hydrogel obtained after crushing through pepsin digestion infiltration or being filled into step
(3) gained three-dimensional framework, is then loaded into the outer tube of the Electrospun material, the peripheral nerve bracket is made.
Later, peripheral nerve bracket is freeze-dried, peripheral nerve bracket is observed by scanning electron microscope (SEM)
Macro, microstructure, as shown in Figure 2.
Finally, it should be noted that the above embodiments are merely illustrative of the technical solutions of the present invention rather than protects to the present invention
The limitation of range is protected, although the invention is described in detail with reference to the preferred embodiments, those skilled in the art should
Understand, it can be with modification or equivalent replacement of the technical solution of the present invention are made, without departing from the essence of technical solution of the present invention
And range.
Claims (9)
1. a kind of peripheral nerve bracket based on 3D printing, which is characterized in that the peripheral nerve bracket includes outer tube and sets
Filler in the outer tube, the filler are three-dimensional frameworks made of gauze curling, and the gauze is using biology ink
Water is made.
2. peripheral nerve bracket according to claim 1, which is characterized in that the outer tube is made of Electrospun.
3. peripheral nerve bracket according to claim 1, which is characterized in that the gauze is made of 3D printing method.
4. peripheral nerve bracket according to claim 1, which is characterized in that the bio-ink contains acrylic double bond end
At least one of hydrogel, natural material and the de- cell hydrogel of tissue of base modified PE G preparation.
5. peripheral nerve bracket according to claim 4, which is characterized in that the natural material is acrylic acid or norborneol
Alkene modified hyaluronic acid, gelatin or collagen.
6. peripheral nerve bracket according to claim 4, which is characterized in that the tissue is peripheral nerve, spinal cord, small intestine
Submucosa, umbilical cord, placenta or amnion.
7. peripheral nerve bracket according to claim 1, which is characterized in that being perfused or be impregnated on the three-dimensional framework can
Promote the gel or solution of axon growth or vascularization.
8. peripheral nerve bracket according to claim 1 or claim 7, which is characterized in that be perfused or infiltrate on the three-dimensional framework
The water for thering is the peripheral nerve in solution or the pig source containing β-NGF to obtain after taking off cell, crushing through pepsin digestion
Gel.
9. a kind of preparation method of the peripheral nerve bracket based on 3D printing, which is characterized in that include the following steps：
(1) outer tube of Electrospun material is provided；
(2) two-dimentional gauze is prepared using with temperature, the ink of ultraviolet light sensitive characteristic and 3D printing method, wherein 3D is beaten
Printing barrel temperature is 24~28 DEG C, and the control of forming area temperature is 4~12 DEG C；
(3) two-dimentional gauze obtained by step (2) is kept to use light intensity for 0.1~3mv/cm in above-mentioned low temperature environment2365nm UV
Irradiate 8s~2min；Then, by crimping or cutting superposition, three-dimensional framework is made；
(4) using concentration for the solution of the nervegrowthfactor-β-NGF of the μ of 100pg/ml~10 g/ml or/and mass concentration is 0.1
The hydrogel infiltration or perfusion that~10% pig source peripheral nerve obtains after taking off cell, crushing through pepsin digestion
To three-dimensional framework obtained by step (3), then it is loaded into the outer tube of the Electrospun material, the peripheral branches is made
Frame.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111046590A (en) * | 2019-12-31 | 2020-04-21 | 北京理工大学 | Controllable processing method of biological micro-scaffold for inducing directional growth of nerve cells |
| CN111281599A (en) * | 2020-03-19 | 2020-06-16 | 中国海洋大学 | Enhanced artificial nerve conduit and preparation method and application thereof |
| CN111297513A (en) * | 2020-03-19 | 2020-06-19 | 中国海洋大学 | Artificial nerve conduit loaded with trophic factors and preparation method and application thereof |
| CN113181428A (en) * | 2021-04-26 | 2021-07-30 | 右江民族医学院附属医院 | Preparation method of spinal cord injury repair material and tissue engineering scaffold |
| WO2022226590A1 (en) * | 2021-04-27 | 2022-11-03 | Orthocell Limited | Epineurium repair device and methods of use thereof |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085393A (en) * | 2011-01-26 | 2011-06-08 | 东华大学 | Biodegradable nerve conduit with bilayer structure and preparation method thereof |
| CN104645412A (en) * | 2015-01-28 | 2015-05-27 | 南方医科大学 | Preparation method of bionic artificial nerve scaffold established by collagen |
| CN106730010A (en) * | 2017-01-03 | 2017-05-31 | 广州新诚生物科技有限公司 | Acellular nerve hydrogel is used to prepare the purposes of peripheral nerve injury remediation composition |
| CN106913393A (en) * | 2015-12-28 | 2017-07-04 | 山东国际生物科技园发展有限公司 | A kind of artificial neuron support and preparation method and application |
-
2018
- 2018-06-22 CN CN201810657502.XA patent/CN108853583A/en active Pending
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102085393A (en) * | 2011-01-26 | 2011-06-08 | 东华大学 | Biodegradable nerve conduit with bilayer structure and preparation method thereof |
| CN104645412A (en) * | 2015-01-28 | 2015-05-27 | 南方医科大学 | Preparation method of bionic artificial nerve scaffold established by collagen |
| CN106913393A (en) * | 2015-12-28 | 2017-07-04 | 山东国际生物科技园发展有限公司 | A kind of artificial neuron support and preparation method and application |
| CN106730010A (en) * | 2017-01-03 | 2017-05-31 | 广州新诚生物科技有限公司 | Acellular nerve hydrogel is used to prepare the purposes of peripheral nerve injury remediation composition |
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN111046590A (en) * | 2019-12-31 | 2020-04-21 | 北京理工大学 | Controllable processing method of biological micro-scaffold for inducing directional growth of nerve cells |
| CN111281599A (en) * | 2020-03-19 | 2020-06-16 | 中国海洋大学 | Enhanced artificial nerve conduit and preparation method and application thereof |
| CN111297513A (en) * | 2020-03-19 | 2020-06-19 | 中国海洋大学 | Artificial nerve conduit loaded with trophic factors and preparation method and application thereof |
| CN113181428A (en) * | 2021-04-26 | 2021-07-30 | 右江民族医学院附属医院 | Preparation method of spinal cord injury repair material and tissue engineering scaffold |
| WO2022226590A1 (en) * | 2021-04-27 | 2022-11-03 | Orthocell Limited | Epineurium repair device and methods of use thereof |
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